9. Venous Access
METHODS Literature Search
Timeframe: Publications from 1992 until 2004, single publi-cations from 1981 were considered.
Type of publications: original articles, case-control and cohort studies, randomised trials, meta-analyses, systematic reviews, case studies.
Key Words: catheterisation, catheter, Broviac, Hickman, ultrasound, replacement, complications, bacteraemia, parenteral nutrition, central venous catheter, central line, venous access, heparin, catheter handling, skin hygiene, dressing type, frequency of dressing change, intravenous infusions, catheter infections.
Language: English, French.
VENOUS ACCESS Introduction
The use of central venous catheters (CVCs) to provide venous access has become increasingly common for the purpose of administration of different treatment regi-mens, intravenous nutrition and blood products, prevent-ing at the same time trauma associated with repeated punctures. However, their insertion and usage may be associated with complications. Therefore, educated per-sonnel should insert and look after the catheter, provide aseptic conditions in handling the catheter and maintain appropriate skin hygiene around the catheter.
The terminology used to identify various types of catheters differs and may be confusing. However, for the purpose of providing parenteral nutrition (PN), it is nec-essary to differentiate peripheral from central venous access, and among the central venous catheters (CVC) those non-tunnelled i.e. inserted either peripherally (PICC) or directly percutaneously, from tunnelled central catheters. Intravascular Catheters for Parenteral Nutrition
Types of Catheters
Establishing a peripheral venous access is defined as placement of a needle or short catheter in a subcutaneous vein. As phlebitis of peripheral veins can be expected when the osmolality of i.v. solution exceeds 600 mOsm (1 (LOE 21)), peripheral veins are only used for short-term venous access and for providing partial nutritional supplementation. Initiation of full PN requires the place-ment of a CVC. Central venous access is obtained by advancing a catheter into the superior or inferior vena cava or outside of the right atrium. A percutaneously
placed CVC can be inserted directly through one of the deep veins e.g. subclavian, internal jugular, or femoral. Another option is a peripherally inserted central catheter (PICC), which uses a subcutaneous vein as the entry site to reach the central vein (2,3, LOE 3). For long-term continuous or frequent use, tunnelled catheters, such as Broviac or Hickman CVC’s, are usually placed ((4) (LOE 21), (5) (LOE 21)). The extra vascular portion of these devices is tunnelled subcutaneously. A Dacron cuff is implanted subcutaneously, allowing for better fixation and, because of the distance between the insertion site and the entry into the vein, inhibits migration of micro organisms ((6) (LOE 11); (7) (LOE 21)). Totally im-plantable devices i.e. subcutaneous ports, are ideal for long-term but intermittent vascular access. Each port access requires needle sticking and, therefore, their value for PN is limited ((8) (LOE 21)).
Catheter Material
Catheters made of stiffer material (polyvinylchloride, polypropylene, polyethylene) are easier to insert, but have been associated with more infectious and mechan-ical complications ((9) (LOE 21)). Softer catheters (silicone and polyurethane) are less thrombogenic and less traumatic, and are, therefore, preferable for long-term use ((10) (LOE 21); (11) (LOE 3)).
In adults, catheters coated with chlorhexidine/silver sulfadiazine and minocyline/rifampin, on both the external and internal surfaces, reduce the rate of catheter-related bloodstream infections ((12) (LOE 11), (13) (LOE 11)). In adults, in settings associated with high risk for infections (e.g. ICU patients), the use of these expensive devices might be cost-effective, and may justify the possible emer-gence of resistant bacterial strains ((14) (LOE 11)).
Recommendation
Peripherally inserted central catheters (PICC’s) and tunnelled central venous catheters (CVCs) should be used preferentially to provide central venous access in neonates and children receiving prolonged PN. GOR C
Recommendation
Silicone and polyurethane coated with hydromers are preferable materials for catheters used for long-term PN. GOR C
Insertion Sites
When a CVC is inserted into a deep vein, the choice of insertion site depends on the expected risk for thrombo-phlebitis, for mechanical complications and/or for catheter infection, which may all be specific for each insertion site.
The subclavian site is widely accepted as the preferred site of insertion, as it causes less patient discomfort, and in adult patients, carries the lowest risk of infection risk ((15) (LOE 21), (16) (LOE 12)).
In children, the subclavian site is also the most common site for insertion of tunnelled CVC’s, although it has not been proven to carry less infection risk ((17) (LOE 11); (18) (LOE 3)); (5) (LOE 21)). Cannulation of the subclavian vein might be associated with danger-ous complications such as pneumothorax and haemo-thorax. However, with adequate experience of the physician performing the procedure and sufficient sedation or general anaesthesia, the risk of mechanical complica-tions in children at subclavian sites does not exceed the rate of complications at other insertion sites ((19) (LOE 3); (20) (LOE 3)). In contrast to adults, femoral catheters in children have not been shown to have a higher incidence of mechanical and infectious complications compared to jugular and subclavian sites ((21) (LOE 21); (22) (LOE 3); (17) (LOE 11); (23) (LOE 3); (24) (LOE 3)). However, femoral access is uncomfortable for the child while the consequences of potential inferior vena cava thrombosis may be severe. The insertion of a CVC is customarily followed by chest radiography for verification of the catheter’s course and the position of its tip. In addition, ECG-monitoring may be helpful.
Positioning of the Catheter Tip
Cardiac tamponade is a rare but life threatening com-plication of CVC’s ((25) (LOE 3), (26) (LOE 3)). There may be an increased risk of pericardial tamponade when the tip is placed within the heart outline as seen on chest x-ray ((27) (LOE 3), (28) (LOE 4)). It is, therefore, advisable that the CVC tip lies outside the pericardial sac and should be repositioned whenever possible ((27) (LOE 3); (29) (LOE 3)). The preferable position for the
catheter tip on the chest x-ray is at least 0.5 cm outside the cardiac outline for the small infant, and 1.0 cm in larger infants ((28) (LOE 4)). For older children and adults, positioning above the carina, which can be used as an anatomic landmark, suggests that the catheter tip of the CVC placed in the superior vena cava is likely to be outside the pericardial sack ((30) (LOE 4)). The risk of perforation depends on the angle of the catheter and the vessel wall; therefore, the catheter should be parallel with the long axis of the vein ((31) (LOE 4)).
Ultrasonic Guidance
The ultrasound-guided technique can significantly increase the precision and safety of CVC placement in children and newborns when the internal jugular vein is cannulated ((32) (LOE 3); (33) (LOE 3)).
Methods of Insertion
Methods of insertion of CVCs, including tunnelled CVC’s, are percutaneous placement and the surgical cut-down technique. The chance of permanent damage to the vein is increased when the cut-down method is used ((34) (LOE 21)). The percutaneous insertion method is as effective as the surgical cut-down ((34) (LOE 21), (35) (LOE 21)).
Also, the diameter of the inserted catheter should be as small as possible to minimize the risk of scaring, Statements and Recommendations
In infants and children, in contrast to adults, femoral catheters do not show a higher incidence of mechanical and infectious complications in comparison with jugular and subclavian sites. LOE 2
In children the risk of mechanical complications of subclavian venous access does not exceed the rate of complications with other insertion sites under appropriate conditions of insertion. GOR C
Statement and Recommendations
The CVC tip should lie outside the pericardial sac to avoid the risk of pericardial tamponade. GOR D In small infants the catheter tip of a jugular or subclavian CVC should lie at least 0.5 cm outside the cardiac outline on a chest x-ray, while in older/larger infants that distance should be at least 1.0 cm. The catheter tip of a femoral catheter should lie above the renal veins. GOR D In older children, as in adults, positioning above
the carina suggests that the catheter tip lying in the superior vena cava is likely to be outside the pericardial sack. LOE 4
The risk of perforation increases with the acute angle of the catheter and the vessel wall. Therefore, the catheter should be parallel with the long axis of the vein. GOR D
Statement
stricture, occlusion and distortion of the cannulated vein ((36) (LOE 3)).
In adults, administration of antibiotics before CVC insertion or the CVC flush with a combination of an anti-biotic and heparin has been justified ((37) (LOE 111)). In children, the use of vancomycin concurrent with catheter insertion was associated with decreased in-cidence of CVC blood stream infections ((38) (LOE 21), (39) (LOE 21)).
Umbilical Catheters
In neonates, umbilical vessels may be directly accessed in the first few days of life and, therefore, this route of central venous approach can regularly be used for PN. However, the risk of expected thrombotic com-plications limits the use of umbilical catheters to being a bridge procedure while awaiting placement of a long-term device ((40) (LOE 21); (41) (LOE 21); (42) (LOE 21); (43) (LOE 21)). Umbilical artery catheters placed above the diaphragm are associated with a lower inci-dence of vascular complications ((44) (LOE 11)).
Replacement Schedule
Routine replacement of CVC’s and PICC’s does not prevent catheter-related bloodstream infections ((45) (LOE 21); (46) (LOE 11); (47) (LOE 11)). Function-ing CVC’s without evident complications should, there-fore, be left in place as long as needed. A malfunctioning CVC can be replaced using a guide-wire insertion
technique ((47) (LOE 11)). This technique lowers the risk of mechanical complications associated with CVC replacement and may make chest radiography unneces-sary in adult patients ((48) (LOE 21)). Replacement over the guide-wire should, however, not be performed in the presence of bacteraemia or in patients suspected to have catheter related infection ((47) (LOE 11)).
Alternative Sites for CVC Placement
CVC complications following multiple catheterisa-tions can lead to thrombosis and depletion of commonly used venous access sites. Alternative approaches in these children should be regarded as rescue accesses and in-clude the transhepatic, translumbar, intercostal ((49) (LOE 3); (50) (LOE 3) (51) (LOE 3)), and the arterio-venous fistula (52). Preferences among the alternative sites depend on the experience of the physician perform-ing the procedure and the condition of each individual patient.
Lines Designated Only to PN
In order to prevent catheter related infections, several recommendations have been suggested, including dedi-cating the CVC to PN only, i.e. not using it for blood sampling or for delivering other fluids or drugs ((53) (LOE 211)). However, many of the patients who re-quire PN are critically ill and have poor venous access, so the use of multiple lumen catheters allows additional access ports for the provision of compatible medications. Double and triple lumen catheters seem to be associated with an increased risk of bacteraemia compared to single lumen devices ((54) (LOE 21); (55) (LOE 211); (56) (LOE 211)). They also seem to be more prone to the development of catheter-related sepsis, possibly because of more frequent catheter manipulations ((53) (LOE 211); (57) (LOE 21); (58) (LOE 11)). The rate of catheter related sepsis has been reported to be as high as 10–20% compared to 0–5% associated with single lumen catheters ((53) (LOE 211); (59) (LOE 11); (58) (LOE 11)).
In contrast, some adult studies showed that the use of multi lumen catheters for PN is safe and that they did not result in an increased incidence of catheter related sepsis ((60) (LOE 21); (61) (LOE 21); (62) (LOE 211); (63) (LOE 11); (64) (LOE 211); (65) (LOE 11)). It is Statement and Recommendation
Percutaneous, radiologically controlled, insertion method is equally effective as surgical cut-down, and carries less risk of damaging the vein. LOE 2+ CVC placement should be done under strict aseptic environment, and preferably under general anesthesia and by an experienced team. GOR D
Statements
In neonates, umbilical vessels can be used for PN. The risk of complications increases if umbilical artery catheters are being left in place for more than 5 days. LOE 2++
The risk of complications increases if umbilical venous catheters are being left in place for more than 14 days. LOE 1+
Umbilical artery catheters placed above the diaphragm are associated with a lower incidence of vascular complications. LOE 1+
Recommendations
CVC’s and PICC’s should not be replaced routinely. GOR B
important to emphasize that in most of these studies ei-ther one port of the multiple lumen catheter was reserved only for PN, or the catheter was limited to administration of compatible medications and solutions while adminis-tration of blood products, withdrawal of blood and mea-surement of central venous pressure were prohibited. The authors concluded that PN can safely be given through multiple lumen catheters provided that these measures are strictly followed ((63) (LOE 11), (64) (LOE 211), (65) (LOE 11)).
Catheter Heparinisation
In children, central venous lines are the most frequent cause of venous thromboembolism and are responsible for over 80% of venous thromboembolism in newborns and 40% in other children ((66) (LOE 211); (67) (LOE 21)). Furthermore, CVC related thrombosis is, alongside sepsis, the most common clinically significant compli-cation of PN ((68) (LOE 21), (69) (LOE 21)). Factors that have been associated with initiation and propagation of thrombosis include endothelial damage during cathe-ter placement, blood vessel occlusion, low flow states, blood stasis, turbulent flow, blood hyperviscosity or hyper-coagulability, patients’ and infusates’ characteristics and catheter composition ((70) (LOE 211), (71) (LOE 11)). In an attempt to prolong the duration of catheter patency and to prevent venous thromboembolism as well as its potentially fatal complications, the use of heparin has been suggested ((72) (LOE 21), (73) (LOE 21)). Heparin is a glycosaminoglycan with anticoagulant effects mediated largely through its interaction with antithrom-bin III that markedly accelerates its ability to inactivate coagulation enzymes (thrombin, factor Xa and factor IXa) ((74) (LOE 211)).
In providing PN, heparin could have the following potential benefits:
1. anticoagulant action – besides reducing fibronectin deposition, heparin makes the line hydrophobic, giving it a negative charge, both of which may influence the catheter thrombogenicity ((70) (LOE 211); (75) (LOE 11); (76) (LOE 111));
2. prevention of infection – a thrombus might serve as a nidus for microbial colonization of intravascular catheters ((77) (LOE 11); (78) (LOE 211)). Heparin bonded catheters were reported to diminish bacterial adherence ((79) (LOE 211)), as well as to lower the incidence of positive blood cultures, presumably related to the lower incidence of thrombosis ((70) (LOE 211)) or to a reduced number of micro-organisms attached to the surface of the catheter ((75) (LOE 11));
3. activation of lipoprotein lipase - given in infusion, heparin also activates lipoprotein lipase and increases lipolysis and reesterification of infused triglycerides, but has no effect on lipid oxidation and net energy gain ((80) (LOE 11); (81) (LOE 11); (82) (LOE 211); (83) (LOE 211)).
There are certain possible complications related to the use of heparin in PN, notably bleeding, heparin induced thrombocytopenia, allergic reactions, osteoporosis, which all may result in serious long-term sequelae ((84) (LOE 21); (85) (LOE 111); (74) (LOE 211); (86) (LOE 3)). In addition, neonates are unique in their sensitivity and resistance to heparin and in their higher propensity to develop intracranial haemorrhage ((87) (LOE 22); (88) (LOE 21)). Both low molecular weight heparin and heparin used as a catheter coating agent are associated with these complications, although the risk associated with low molecular weight heparin is reduced compared to unfractionated heparin ((85) (111), (89) (211), (90) (3)).
Another risk of adding heparin to PN solutions is the possibility of inducing incompatibility. Calcium and heparin can destabilize lipid emulsions leading to floccu-lation and separation of the lipid from the aqueous phase (91). However, this is unlikely if low heparin concentrations are used (0.5 to 1 U/ml) ((92) (LOE 21)). Together with minimizing their contact time (having the delivery tube between the point of mixing lipid and amino acid solutions as short as possible), co-administration of vitamin prepara-tions will further decrease this effect ((92) (LOE 21)).
The current attitude towards prescribing heparin, therefore, differs with regard to whether to use it at all or not, and if yes, in what way (as a flush or in PN infusion), how often and how much. In practice, wide variations are observed in volumes of provided heparin ranging from 5 to 10 ml ((93) (LOE 21), (94) (LOE 11), (95) (LOE 12)), concentration of heparin ranging from 10 U/ml to 200 U/ml ((93) (LOE 21), (94) (LOE 11), (69) (LOE 21)) as well as in the frequency of Statements and Recommendations
Where possible a central venous line should be dedicated for the administration of PN. GOR B If a CVC is used to administer PN, use a catheter
with the minimal number of ports or lumens es-sential for the management of the patient. GOR B If a multi lumen catheter is used to administer PN, designate one port exclusively for PN. Blood administration and central intravenous pressure monitoring from the designated line should be avoided. GOR B (from adult studies)
heparinisation that ranges from daily infusions ((96) (LOE 211)) to flushes once or twice daily ((94) (LOE 11); (97) (LOE 21)) to once a week ((98) (LOE 22)) or even once in three weeks ((99) (211)). Boluses in children frequently contain 200 to 300 U of heparin, and for infants weighing less than 10 kg, a dose of 10 U/kg is frequently used ((89) (211)). In a meta-analysis evaluating the benefit of heparin prophylaxis (3 U/ml in PN solution; 5000 U every 6 to 12 hours flush or 2500 U of low molecular weight heparin subcutaneously) in patients with CVC’s, the risk of central venous throm-bosis was significantly reduced. Although bacterial colonization was also decreased, no substantial differ-ence in the rate of catheter related infection was observed ((100) (LOE 11)). Of the 11 studies included in this meta-analysis only one was performed in the paediatric population. This randomised cross-over study showed that there was no significant difference in the incidence of blocked catheters or other complications between the group of paediatric patients whose CVC’s were flushed twice daily with a heparin solution and the group with isotonic saline flushes applied once a week ((94) (LOE 11)).
Another randomized double blind trial on paediatric patients demonstrated that the use of normal saline com-pared to heparinised infusion (saline1 1U of heparin/ml) did not significantly adversely affect patency of CVC’s ((101) (LOE 11)). The proportion of non patent catheters was smaller in the heparinised group but the difference was not statistically significant. However, both studies had a small sample size and thus not enough statistical power to draw definitive conclusions.
Shah et al performed a systematic review on the pro-phylactic use of heparin for prevention of complications related to peripherally placed percutaneous central venous catheters in neonates but not even one well designed randomized controlled trial was found. Therefore, the routine use of heparin for this purpose could not be recommended ((102) (LOE 111)).
Later, Kamala et al performed a randomized, double-blind controlled study of heparin infusion (1 U/ml) for prevention of blockage of peripherally inserted central catheter in neonates and found no significant difference in the incidence of blocked catheters, catheter sepsis, hyper-trigliceridaemia, hyperbilirubinaemia, coagulopathy or intraventricular haemorrhage between treated and un-treated group ((103) (LOE 12)). However, the study sample was again too small and with a high risk of bias.
Skin hygiene, Dressing Methods and Frequency of Dressing Changes
Skin Antisepsis and Hygiene
Extensive studies have been done to determine which antiseptic solution is the most effective way of removing micro organisms from the skin surface before catheter insertion and during catheter care. The best option appears to be 2% chlorhexidine, which was found to significantly reduce catheter related infections (CRI) ((104) (LOE 11); (105) (LOE 211)). In a comparison of 2% chlorhexidine to povidone-iodine and 70% alcohol, it was shown that the two latter solutions were associated with a fourfold higher incidence of CRI ((106) (LOE 11)). However, when 0.5% chlorhexidine was applied and compared to 10% povidone-iodine no difference in prevention of catheter related bacteriemia could be demonstrated ((107) (LOE 11)).
Dressing Methods and Frequency of Dressing Changes
Apart from providing protection from external contam-ination, the purpose of the dressing is to secure the CVC and to prevent dislodgement and trauma. Traditionally it was common to dress the CVC site with dry gauze and tape. This method gave way to transparent polyurethane film dressings, defined as dressing composed of a thin Statements and Recommendation
There is no proven benefit of heparin for the prevention of thrombotic occlusion of CVC’s under regular use in children. Therefore its routine use is not recommended. LOE 12
With respect to CVC’s not in regular use, in adults, flushing with 5 to 10 U/ml of heparinised saline once to twice weekly was useful in maintaining CVCs patency and is recommended. GOR D
Routine use of heparin has not been shown to be useful in prevention of complications related to peripherally placed percutaneous CVCs in neo-nates. LOE 12
Recommendations
Before insertion of an intravascular device and for post-insertion site care, a clean skin should be disinfected. Application of 2% chlorhexidine is preferred, rather then 10% povidone-iodine or 70% alcohol. GOR A
Antiseptic solution should remain on the inser-tion site and air dry before catheter inserinser-tion or dressing application. GOR D
polyurethane membrane coated with a layer of acrylic adhesive. Potential advantages of these dressings include improved security of the catheter, visibility of the wound site, provision of an effective barrier to micro organisms and, therefore, less frequent need for dressing changing. However, there is a concern that the polyurethane dressings may increase the skin surface humidity, resulting in increased colonization of the micro organisms at the catheter insertion site ((108) (LOE 11); (109) (LOE 11); (110) (LOE 11)), thereby increasing the risk of catheter related infections ((108) (LOE 11), (111) (LOE 21)).
Numerous studies have investigated the differences between dressing regimens (incidence of CVC-related infection, catheter security, dressing condition and ease of application, tolerance to dressing materials). The first meta-analysis that compared the effect of two different dressing types concluded that the risk of catheter tip infection, but not sepsis, was significantly increased with transparent CVC dressings compared to gauze and tape ((113) (LOE 12)). However, according to the recent Cochrane Systematic Review by Gillies, et al., several factors could have biased the results of the above men-tioned meta-analysis (114). This review failed to dem-onstrate any difference in the incidence of infectious complications between any dressing types compared (gauze and tape vs Opsite IV300, Opsite vs Opsite IV300, Tegaderm vs Opsite IV300, Tegaderm vs Opsite). As most of the included studies were performed on a small patient sample, they probably did not have a sufficient power to detect any differences between the groups. The authors, therefore, concluded that at this stage the choice of dress-ing for CVC can be based on patient preference, while the answer on ‘‘What is the appropriate dressing to use for CVC’’ requires further research ((114) (LOE 111)).
Most of the studies mentioned have been done in adult populations, as there are very few studies involving chil-dren. A trial looking at the prevention of CVC infections in neonates concluded that the use of alcohol for cuta-neous antiseptics with a subsequent placement of a chlorhexidine-impregnated dressing (Biopatch) over the insertion site of CVC (which should be left on for up to 7 days between dressing changes), provides protection against catheter tip colonisation. The rates of catheter related blood stream infections and blood stream infec-tions without a source were, however, similar among treatment groups. A substantial risk of contact dermatitis at the dressing site may limit its use in low birth weight infants in the first 2 weeks of life ((115) (LOE 11)).
Taylor et al, conducted a study on paediatric population with the aim of determining whether ‘‘microbial growth increased significantly over time when occlusive dressings were used to cover CVC insertion sites’’. They concluded that occlusive dressings, changed every 3 to 4 days using an aseptic technique, are safe and efficient and provide a barrier that prevents CVC exit site contamination with children’s body fluids, food, and surgical wound drain-age, and helps to anchor and stabilise the tubing ((116)
(LOE 22)). Although tunnelled central venous catheters with well-healed exit sites do not require any dressing to prevent dislodgement, it is useful to have them covered. Concerning catheter submerging, according to Robbins et al, swimming does not increase the risk of catheter-related infections in children with tunnelled catheters ((117) (LOE 22)).
The use of topical antibiotic ointments to clean the insertion sites at dressing changes is not recommended, as such ointments are associated with an increased frequency of fungal infections ((118) (LOE 12)), antibiotic resistance ((119) (LOE 3)), and might adversely affect the integrity of polyurethane catheters ((120) (LOE 3), (120) (LOE 3)).
REFERENCES
1. Gazitua R, Wilson K, Bistrian BR, et al. Factors determining peripheral vein tolerance to amino acid infusions. Arch Surg 1979; 114:897–900.
2. Puntis JWL. Percutaneous insertion of central venous feeding catheters. Arch Dis Child 1986;61:1138–40.
3. Thiagarajan RR, Ramamoorthy C, Gettmann T, et al. Survey of the use of peripherally inserted central venous catheters in children. Pediatrics 1997;99:E4.
4. Ladefoged K, Efsen F, Krogh Christoffersen J, et al. Long-term parenteral nutrition. II. Catheter-related complications. Scand J Gastroenterol 1981;16:913–9.
5. Murai DT. Are femoral Broviac catheters effective and safe? A prospective comparison of femoral and jugular venous broviac catheters in newborn infants. Chest 2002;121:1527–30.
Recommendations
Both, sterile gauze 1 tape and various transparent polyurethane film dressings can be used for the catheter site. GOR A
If the catheter site is bleeding or oozing, a gauze dressing is preferable to a transparent, semi-permeable dressing. LOE 4
The catheter-site dressing should be replaced when it becomes damp, loosened, or when inspec-tion of the site is necessary. GOR D
On short term CVC sites dressings should be replaced every 2 days for gauze dressings and at least every 7 days for transparent dressings, except in those paediatric patients in which the risk for dislodging the catheter outweighs the benefit of changing the dressing. GOR B
Topical antimicrobial ointments should not be used routinely at the insertion site as they may promote fungal infection, antimicrobial resis-tance and damage the surface of the catheters. GOR D
6. Timsit JF, Bruneel F, Cheval C, et al. Use of tunneled femoral catheters to prevent catheter-related infection. A randomized, controlled trial. Ann Intern Med 1999;130:729–35.
7. Nahum E, Levy I, Katz J, et al. Efficacy of subcutaneous tunneling for prevention of bacterial colonization of femoral central venous catheters in critically ill children. Pediatr Infect Dis J 2002;21: 1000–4.
8. Flynn PM, Willis B, Gaur AH, et al. Catheter design influences recurrence of catheter-related bloodstream infection in children with cancer. J Clin Oncol 2003;21:3520–5.
9. Sheth NK, Franson TR, Rose HD, et al. Colonization of bacteria on polyvinyl chloride and Teflon intravascular catheters in hospitalized patients. J Clin Microbiol 1983;18:1061–3. 10. Sank A, Chalabian-Baliozian J, Ertl D, et al. Cellular responses to
silicone and polyurethane prosthetic surfaces. J Surg Res 1993;54: 12–20.
11. Polderman KH, Girbes AJ. Central venous catheter use. Part 1: mechanical complications. Intensive Care Med 2002;28:1–17. 12. Maki DG, Stolz SM, Wheeler S, et al. Prevention of central venous
catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. A randomized, controlled trial. Ann Intern Med 1997;127:257–66.
13. Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group. Ann Intern Med 1997;127:267–74.
14. Veenstra DL, Saint S, Sullivan SD. Cost-effectiveness of antiseptic-impregnated central venous catheters for the prevention of catheter-related bloodstream infection. JAMA 1999;282: 554–60.
15. Goetz AM, Wagener MM, Miller JM, et al. Risk of infection due to central venous catheters: effect of site of placement and catheter type. Infect Control Hosp Epidemiol 1998;19:842–5.
16. Merrer J, De Jonghe B, Golliot F, et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001;286:700–7.
17. Venkataraman ST, Thompson AE, Orr RA. Femoral vascular catheterization in critically ill infants and children. Clin Pediatr (Phila) 1997;36:311–9.
18. Sovinz P, Urban C, Lackner H, et al. Tunneled femoral central venous catheters in children with cancer. Pediatrics 2001;107:E104. 19. Johnson EM, Saltzman DA, Suh G, et al. Complications and risks of central venous catheter placement in children. Surgery 1998; 124:911–6.
20. Citak A, Karabocuoglu M, Ucsel R, et al. Central venous catheters in pediatric patients-subclavian venous approach as the first choice. Pediatr Int 2002;44:83–6.
21. Stenzel JP, Green TP, Fuhrman BP, et al. Percutaneous femoral venous catheterizations: a prospective study of complications. J Pediatr 1989;114:411–5.
22. Goldstein AM, Weber JM, Sheridan RL. Femoral venous access is safe in burned children: an analysis of 224 catheters. J Pediatr 1997;130:442–6.
23. Chen KB. Clinical experience of percutaneous femoral venous catheterization in critically ill preterm infants less than 1,000 grams. Anesthesiology 2001;95:637–9.
24. Wardle SP, Kelsall AW, Yoxall CW, et al. Percutaneous femoral arterial and venous catheterisation during neonatal intensive care. Arch Dis Child Fetal Neonatal Ed 2001;85:F119–22.
25. van Engelenburg KC, Festen C. Cardiac tamponade: a rare but life-threatening complication of central venous catheters in children. J Pediatr Surg 1998;33:1822–4.
26. Nowlen TT, Rosenthal GL, Johnson GL, et al. Pericardial effusion and tamponade in infants with central catheters. Pediatrics 2002; 100:137–42.
27. Collier PE, Blocker SH, Graff DM, et al. Cardiac tamponade from central venous catheters. Am J Surg 1998;176:212–4.
28. Darling JC, Newell SJ, Dear PR. Placement of neonatal central venous catheter tips in the right atrium: a practice to be avoided. Arch Dis Child Fetal Neonatal Ed 2001;85:F146.
29. Menon G. Neonatal long lines. Arch Dis Child Fetal Neonatal Ed 2003;88:F260–2.
30. Schuster M, Nave H, Piepenbrock S, et al. The carina as a landmark in central venous catheter placement. Br J Anaesth 2000;85:192–4.
31. Fletcher SJ, Bodenham AR. Safe placement of central venous catheters: where should the tipp of the catheter lie? Br J Anaesth 2000;85:188–91.
32. Amram S, Zeraffatourkine MH, Bourgeois JM, et al. Ultrasound-guided percutaneous central venous catheterization in preterm infants. Ann Pediatr 1995;42:55–9.
33. Asheim P, Mostad U, Aadahl P. Ultrasound-guided central venous cannulation in infants and children. Acta Anaesthesiol Scand 2002;46:390–2.
34. Davis SJ, Thompson JS, Edney JA. Insertion of Hickman’s catheters in total parenteral nutrition: a prospective study of 200 consecutive patients. Am Surg 1984;50:673–6.
35. Nosher JL, Shami MM, Siegel RL, et al. Tunneled central venous access catheter placement in the pediatric population: comparison of radiologic and surgical results. Radiology 1994;192:265–8. 36. Alderson PJ, Burrows FA, Stemp LI, et al. Use of ultrasound to
evaluate internal jugular vein anatomy and to facilitate central venous cannulation in paediatric patients. Br J Anaesth 1993;70:145–8. 37. van de Wetering MD, van Woensel JB. Prophylactic antibiotics
for preventing early central venous catheter Gram positive infec-tions in oncology patients. Cochrane Database Syst Rev 2003; CD003295.
38. Fallat ME, Gallinaro RN, Stover BH, et al. Central venous catheter bloodstream infections in the neonatal intensive care unit. J Pediatr Surg 1998;33:1383–7.
39. Shaul DB, Scheer B, Rokhsar S, et al. Risk factors for early infection of central venous catheters in pediatric patients. J Am Coll Surg 1998;186:654–8.
40. Fletcher MA, Brown DR, Landers S, et al. Umbilical arterial catheter use: report of an audit conducted by the Study Group for Complications of Perinatal Care. Am J Perinatol 1994;11:94–9. 41. Seguin J, Fletcher MA, Landers S, et al. Umbilical venous
catheterizations: audit by the Study Group for Complications of Perinatal Care. Am J Perinatol 1994;11:67–70.
42. Loisel DB, Smith MM, MacDonald MG, et al. Intravenous access in newborn infants: impact of extended umbilical venous catheter use on requirement for peripheral venous lines. J Perinatol 1996; 16:461–6.
43. Boo NY, Wong NC, Zulkifli SS, et al. Risk factors associated with umbilical vascular catheter-associated thrombosis in newborn infants. J Paediatr Child Health 1999;35:460–5.
44. Barrington KJ. Umbilical artery catheters in the newborn: effects of position of the catheter tip. Cochrane Database Syst Rev 2000; 2:CD000505.
45. Eyer S, Brummitt C, Crossley K, et al. Catheter-related sepsis: prospective, randomized study of three methods of long-term catheter maintenance. Crit Care Med 1990;18:1073–9. 46. Cobb DK, High KP, Sawyer RG, et al. A controlled trial of
scheduled replacement of central venous and pulmonary-artery catheters. N Engl J Med 1992;327:1062–8.
47. Cook D, Randolph A, Kernerman P, et al. Central venous catheter replacement strategies: systematic review of the literature. Crit Care Med 1997;25:1417–24.
48. Palesty JA, Amshel CE, Dudrick SJ. Routine chest radiographs following central venous recatheterization over a wire are not justified. Am J Surg 1998;176:618–21.
49. Azizkhan RG, Taylor LA, Jaques PF, et al. Percutaneous trans-lumbar and transhepatic inferior vena cava catheters for prolonged vascular access in children. J Pediatr Surg 1992;27:165–9. 50. Cheatham JP, McCowan TC, Fletcher SE. Percutaneous
alternative approach in children with congenital heart disease. Catheter Cardiovasc Interv 1999;46:187–92.
51. de Csepel J, Stanley P, Padua EM, et al. Maintaining long-term central venous access by repetitive hepatic vein cannulation. J Pediatr Surg 1994;29:56–7.
52. Goldstein SL, Baronette S, Gambrell TV, et al. nPCR assessment and IDPN treatment of malnutrition in pediatric hemodialysis patients. Pediatr Nephrol 2002;17:531–4.
53. Pemberton LB, Lyman B, Lander V, et al. Sepsis from triple- vs single-lumen catheters during total parenteral nutrition in surgical or critically ill patients. Arch Surg 1986;121:591–4.
54. Apelgren KN. Triple lumen catheters. Technological advance or setback? Am Surg 1987;53:113–6.
55. Yeung C, May J, Hughes R. Infection rate for single lumen v triple lumen subclavian catheters. Infect Control Hosp Epidemiol 1988; 9:154–8.
56. Lagro SW, Verdonck LF, Borel Rinkes IH, et al. No effect of nadroparin prophylaxis in the prevention of central venous catheter (CVC)-associated thrombosis in bone marrow transplant recipients. Bone Marrow Transplant 2000;26: 1103–6.
57. Hilton E, Haslett TM, Borenstein MT, et al. Central catheter infections: single- versus triple-lumen catheters. Influence of guide wires on infection rates when used for replacement of catheters. Am J Med 1988;84:667–72.
58. Clark-Christoff N, Watters VA, Sparks W, et al. Use of triple-lumen subclavian catheters for administration of total parenteral nutrition. JPEN J Parenter Enteral Nutr 1992;16:403–7. 59. McCarthy MC, Shives JK, Robison RJ, et al. Prospective
evaluation of single and triple lumen catheters in total parenteral nutrition. JPEN J Parenter Enteral Nutr 1987;11:259–62. 60. Kaufman JL, Rodriguez JL, McFadden JA, et al. Clinical
experience with the multiple lumen central venous catheter. JPEN J Parenter Enteral Nutr 1986;10:487–9.
61. Lee RB, Buckner M, Sharp KW. Do multi-lumen catheters increase central venous catheter sepsis compared to single-lumen catheters? J Trauma 1988;28:1472–5.
62. Gil RT, Kruse JA, Thill-Baharozian MC, et al. Triple- vs single-lumen central venous catheters. A prospective study in a critically ill population. Arch Intern Med 1989;149:1139–43.
63. Johnson BH, Rypins EB. Single-lumen vs double-lumen catheters for total parenteral nutrition. A randomized, prospective trial. Arch Surg 1990;125:990–2.
64. Savage AP, Picard M Hopkins CC, et al. Complications and survival of multilumen central venous catheters used for total parenteral nutrition. Br J Surg 1993;80:1287–90.
65. Ma TY, Yoshinaka R, Banaag A, et al. Total parenteral nutrition via multilumen catheters does not increase the risk of catheter-related sepsis: a randomized, prospective study. Clin Infect Dis 1998;27:500–3.
66. Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994;83:1251–7.
67. Schmidt B, Andrew M. Neonatal thrombosis: report of a pro-spective Canadian and international registry. Pediatrics 1995;96: 939–43.
68. Moukarzel AA, Haddad I, Ament ME, et al. 230 patient years of experience with home long-term parenteral nutrition in childhood: natural history and life of central venous catheters. J Pediatr Surg 1994;29:1323–7.
69. Andrew M, Marzinotto V, Pencharz P, et al. A cross-sectional study of catheter-related thrombosis in children receiving total parenteral nutrition at home. J Pediatr 1995;126:358–63. 70. Krafte-Jacobs B, Sivit CJ, Mejia R, et al. Catheter-related
thrombosis in critically ill children: comparison of catheters with and without heparin bonding. J Pediatr 1995;126:50–4. 71. Pottecher T, Forrler M, Picardat P, et al. Thrombogenicity of
central venous catheters: prospective study of polyethylene,
silicone and polyurethane catheters with phlebography or post-mortem examination. Eur J Anaesthesiol 1984;1:361–5. 72. Dollery CM, Sullivan ID, Bauraind O, et al. Thrombosis and
embolism in long-term central venous access for parenteral nutrition. Lancet 1994;344:1043–5.
73. Pollard AJ, Sreeram N, Wright JG, et al. ECG and echocardio-graphic diagnosis of pulmonary thromboembolism associated with central venous lines. Arch Dis Child 1995;73:147–50. 74. Hirsh J, Warkentin TE, Raschke R, et al. Heparin and
low-molecular-weight heparin: mechanisms of action, pharmacokinet-ics, dosing considerations, monitoring, efficacy, and safety. Chest 1998;114:489S–510.
75. Appelgren P, Ransjo U, Bindslev L, et al. Surface heparinization of central venous catheters reduces microbial colonization in vitro and in vivo: results from a prospective, randomized trial. Crit Care Med 1996;24:1482–9.
76. Pierce CM, Wade A, Mok Q. Heparin-bonded central venous lines reduce thrombotic and infective complications in critically ill children. Intensive Care Med 2000;26:967–72.
77. Raad II Luna M, Khalil SA, et al. The relationship between the thrombotic and infectious complications of central venous catheters. JAMA 1994;271:1014–6.
78. Timsit JF, Farkas JC, Boyer JM, et al. Central vein catheter-related thrombosis in intensive care patients: incidence, risks factors, and relationship with catheter-related sepsis. Chest 1998;114:207–13. 79. Goldmann DA, Pier GB. Pathogenesis of infections related to intravascular catheterization. Clin Microbiol Rev 1993;6:176–92. 80. Spear ML, Stahl GE, Hamosh M, et al. Effect of heparin dose and infusion rate on lipid clearance and bilirubin binding in premature infants receiving intravenous fat emulsions. J Pediatr 1988;112:94–8. 81. Roth B, Ekelund M, Fan BG, et al. Effects of heparin and low molecular weight heparin on lipid transport during parenteral feeding in the rat. Acta Anaesthesiol Scand 1996;40:102–11. 82. Chen X, Ruiz J, Boden G. Release, oxidation, and reesterification
of fatty acids from infused triglycerides: effect of heparin. Metabolism 1995;44:1590–5.
83. Shulman RJ, Phillips S. Parenteral nutrition in infants and children. J Pediatr Gastroenterol Nutr 2003;36:587–60. 84. Spadone D, Clark F, James E, et al. Heparin-induced
thrombocy-topenia in the newborn. J Vasc Surg 1992;15:306–11.
85. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330–5. 86. Ranze O, Rakow A, Ranze P, et al. Low-dose danaparoid sodium catheter flushes in an intensive care infant suffering from heparin-induced thrombocytopenia. Pediatr Crit Care Med 2001;2:175–7.
87. Lesko SM, Mitchell AA, Epstein MF, et al. Heparin use as a risk factor for intraventricular hemorrhage in low-birth-weight infants. N Engl J Med 1986;314:1156–60.
88. Vieira A, Berry L, Ofosu F, et al. Heparin sensitivity and resistance in the neonate: an explanation. Thromb Res 1991;63:85–98. 89. Michelson AD, Bovill E, Monagle P, et al. Antithrombotic therapy
in children. Chest 1998;144:748S–69S.
90. Nasuno A, Matsubara T, Hori T, et al. Acute pulmonary thromboembolism induced by prophylactic heparin use and a heparin-coated catheter: a case of heparin-induced thrombocyto-penia and thrombosis syndrome. Circ J 2003;67:96–8.
91. Johnson OL Washington C, Davis SS, et al. The destabilization of parenteral feeding emulsions by heparin. Int J Pharm 1989;53: 237–40.
92. Silvers KM, Darlow BA, Winterbourn CC. Pharmacologic levels of heparin do not destabilize neonatal parenteral nutrition. JPEN J Parenter Enteral Nutr 1998;22:311–4.
94. Smith S, Dawson S, Hennessey R, et al. Maintenance of the patency of indwelling central venous catheters: is heparin necessary? Am J Pediatr Hematol Oncol 1991;13:141–3. 95. Buswell L, Beyea SC. Flushing protocols for tunneled central
venous catheters: an integrative review of the literature. Online J Knowl Synth Nurs 1998;5:U1–9.
96. Hentschel R, Wiescholek U, von Lengerke J, et al. Coagulation-associated complications of indwelling arterial and central venous catheters during heparin prophylaxis - a prospective study. Eur J Pediatr 1999;158:S126–9.
97. Rizzari C, Palamone G, Corbetta A, et al. Central venous catheter-related infections in pediatric hematology-oncology patients: role of home and hospital management. Pediatr Hematol Oncol 1992; 9:115–23.
98. Kelly C, Dumenko L, McGregor SE, et al. A change in flushing protocols of central venous catheters. Oncol Nurs Forum 1992;19: 599–605.
99. Delva R, Gamelin E, Lortholary A, et al. Suppression of heparinization of central venous catheters between cycles of chemotherapy: Results of a phase I study. Support Care Cancer 1998;6:384–8.
100. Randolph AG, Cook DJ, Gonzales CA, et al. Benefit of heparin in central venous and pulmonary artery catheters: a meta-analysis of randomized controlled trials. Chest 1998;113:165–71.
101. de Neef M, Heijboer H, van Woensel JB, et al. The efficacy of heparinization in prolonging patency of arterial and central venous catheters in children: A randomized double-blind trial. Pediatr Hematol Oncol 2002;19:553–60.
102. Shah P, Shah V. Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters. Cochrane Database Syst Rev 2001;CD002772.
103. Kamala F, Boo NY, Cheah FC, et al. Randomized controlled trial of heparin for prevention of blockage of peripherally inserted central catheters in neonates. Acta Paediatr 2002;91:1350–6. 104. Mimoz O, Pieroni L, Lawrence C, et al. Prospective, randomized
trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients. Crit Care Med 1996;24:1818–23.
105. Elliott TS, Tebbs SE. Prevention of central venous catheter-related infection. J Hosp Infect 1998;40:193–201.
106. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991;338:339–43.
107. Humar A, Ostromecki A, Direnfeld J, et al. Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of
central venous catheter infection. Clin Infect Dis 2000;31: 1001–7.
108. Conly JM, Grieves K, Peters B. A prospective randomized study comparing transparent an dry gauze dressings for central venous catheters. J Infect Dis 1989;159:310–9.
109. Wille JC, Blusse van Oud Albas A, Thewessen EA. A comparison of two transparent film-type dressings in central venous therapy. J Hosp Infect 1993;23:113–21.
110. Maki DG, Stolz SS, Wheeler S, et al. A prospective, randomized trial of gauze and two polyurethane dressings for site care of pulmonary artery catheters: implications for catheter manage-ment. Crit Care Med 1994;22:1729–37.
111. Richet H, Hubert B, Nitemberg G, et al. Prospective multicenter study of vascular-catheter-related complications and risk factors for positive central-catheter cultures in intensive care unit patients. J Clin Microbiol 1990;28:2520–5.
112. O’Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-related infections. Pediatrics 2002;110:1–24.
113. Hoffmann KK, Weber DJ, Samsa GP, et al. Transparent poly-urethane film as an intravenous catheter dressing. A meta-analysis of the infection risks. JAMA 1992;267:2072–6.
114. Gillies D, O’Riordan L, Carr D, et al. Gauze and tape and transparent polyurethane dressings for central venous catheters. Cochrane Database Syst Rev 2003;CD003827.
115. Garland JS, Alex CP, Mueller CD, et al. A randomised trial comparing Povidone-Iodine to a Chlorhexidine Gluconate-im-pregnated dressing for prevention of central venous catheter infections in neonates. Pediatrics 2001;107:1431–6.
116. Taylor D, Myers ST, Monarch K, et al. Use of occlusive dressings on central venous catheter sites in hospitalized children. J Pediatr Nurs 1996;11:169–74.
117. Robbins J, Cromwell P, Korones DN. Swimming and central venous catheter-related infections in the child with cancer. J Pediatr Oncol Nurs 1999;16:51–6.
118. Maki DG, Band JD. A comparative study of polyantibiotic and iodophor ointments in prevention of vascular catheter-related infection. Am J Med 1981;70:739–44.
119. Zakrzewska-Bode A, Muytjens HL, Liem KD, et al. Mupirocin resistance in coagulase-negative staphylococci, after topical prophylaxis for the reduction of colonization of central venous catheters. J Hosp Infect 1995;31:189–93.
120. Rao SP, Oreopoulos DG. Unusual complications of a polyurethane PD catheter. Perit Dial Int 1997;17:410–2.
